| Co-Investigator(Kenkyū-buntansha) |
FUKUI Roh Hirosaki University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (70241479)
SATOH Hisashi Hirosaki University, University Hospital, Instructor, 医学部附属病院, 助手 (90311539)
KUSUMI Tomomi Hirosaki University, School of Medicine, Instructor, 医学部, 助手 (90322932)
|
|---|
| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Research Abstract |
In this study, we investigated biological responses, including signal transduction, of osteoblasts with the application of mechanical stress. Since it was found that the application of 7%, 0.25 Hz cyclic tensile strain (CTS) once a day for 4 hrs for three successive days was induced nitric oxide (NO), p38MAPK activation, the increase of OPG production, and the decrease of sRANKL release from osteoblasts before, analyzes on synthesis of OPG and RANKL in osteoblasts with the application of CTS was examined after the pretreatment with NO donor (NOC18), NO synthase inhibitor (L-NMMA), or p38MAPK inhibitor (SB250380).
1.Analyzes on the relationship between NO and synthesis of OPG and RANKL : Pretreatment with NOCl8 (0.1,1,10μg/ml) or L-NMMA (1,10,100μg/ml) did not affect synthesis of OPG and RANKL from stationary osteoblasts (5 x 10^4cells/ml). On the other hand, synthesis of OPG and sRANKL from osteoblasts with the application of CTS was also not affected by pretreatment with NOCl8 or L-NMMA.
2.Analyzes on the relationship between p38MAPK activation and synthesis of OPG and RANKL : OPG production in stationary osteoblasts dose-dependently decreased with pretreatment of SB250380 (10^<-7>, 10^<-6>, 10^<-5> μM). OPG production from osteoblasts with the application of CTS was dose-dependently inhibited by SB250380 and inhibition of sRANKL release by the application of CTS was dose-dependently abrogated by SB250380. Furthermore, since the levels of mRNA expression of OPG and RANKL in osteoblasts in such application were examined with real-time RT-PCR, similar results were obtained.
3.Conclusions : It was shown that p38 MAPK activation playd an important role in regulating on synthesis of OPG and RANKL in osteoblasts with the application of mechanical stress on bone remodeling, although NO induced by the application of CTS did not affect synthesis of OPG and RANKL.
As next study, we will examine signal transduction above and below p38MAPK pathway.
|
